Patients in ECHELON-1 were randomized to receive either a combination of
ADCETRIS+AVD (Adriamycin, vinblastine, dacarbazine) or ABVD (Adriamycin,
bleomycin, vinblastine, dacarbazine), a recognized standard of care for
frontline Hodgkin lymphoma. The results of the ECHELON-1 trial
demonstrated that combination treatment with ADCETRIS resulted in a
statistically significant improvement in modified PFS versus the control
arm as assessed by an Independent Review Facility (hazard ratio=0.770;
p-value=0.035). The two-year modified PFS rate for patients in the
ADCETRIS arm was 82.1 percent compared to 77.2 percent in the control
arm. Interim analysis of overall survival (OS), the key secondary
endpoint, also trended in favor of the ADCETRIS+AVD arm. An abstract
will be submitted for data presentation at the American Society of
Hematology (ASH) annual meeting, December 9-12, 2017, in Atlanta, Ga.

The safety profile of ADCETRIS+AVD in the ECHELON-1 trial was consistent
with that known for the single-agent components of the regimen. There
was an increased incidence of febrile neutropenia and peripheral
neuropathy in the ADCETRIS+AVD arm. Febrile neutropenia was reduced
through the use of prophylactic growth factors in a subset of patients,
and peripheral neuropathy was managed through dose modifications. The
control arm had an increased rate and severity of pulmonary toxicity.

“We are excited about the positive result which shows a statistically
significant improvement in the primary endpoint of modified PFS,” said
Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic
Area Unit, Takeda Pharmaceutical Company. “The results of this trial
signify an important step forward in the development of ADCETRIS and
have the potential to change the treatment approach of frontline
advanced Hodgkin lymphoma.”

“The outcome of the Phase 3 ECHELON-1 trial represents a significant
milestone for the Hodgkin lymphoma community,” said Clay Siegall, Ph.D.,
President and Chief Executive Officer of Seattle Genetics. “Seattle
Genetics’ goal is to establish ADCETRIS as the foundation of care for
CD30-expressing lymphomas, including Hodgkin lymphoma. Notably, this is
the first clinical trial in frontline advanced Hodgkin lymphoma to show
superior efficacy of a regimen that eliminates bleomycin.”

Takeda and Seattle Genetics plan to submit these results to regulatory
authorities for approval in their respective territories.

ECHELON-1 Phase 3 Clinical Trial Design

The randomized, open-label, Phase 3 trial is investigating ADCETRIS+AVD
versus ABVD as frontline therapy in patients with advanced classical
Hodgkin lymphoma. The primary endpoint is modified progression-free
survival per Independent Review Facility assessment using the Revised
Response Criteria for Malignant Lymphoma. Modified PFS is defined as the
time to progression, death or receipt of additional anticancer therapy
for patients who are not in complete response after completion of
frontline therapy per Independent Review Facility. This endpoint was
chosen as it provides a clearer picture of the efficacy of frontline
chemotherapy and eliminates the confounding impact of salvage and
consolidation chemotherapies and radiotherapy. Secondary endpoints
include overall survival, complete remission and safety. The
multi-center trial was conducted in North America, Europe, South
America, Australia, Asia and Africa. The study enrolled 1,334 patients
who had a histologically-confirmed diagnosis of Stage III or IV
classical Hodgkin lymphoma and had not been previously treated with
systemic chemotherapy or radiotherapy. The ECHELON-1 trial is being
conducted under a Special Protocol Assessment (SPA) agreement from the
U.S. Food and Drug Administration (FDA) and the trial also received
European Medicines Agency (EMA) scientific advice.

Please see Important Safety Information at the end of this press
release.

Seattle Genetics Conference Call Details

Seattle Genetics' management will host a conference call and webcast to
discuss this announcement. The event will be held today at 5:30 a.m.
Pacific Time (PT) / 8:30 a.m. Eastern Time (ET). The live event will be
available from Seattle Genetics' website at http://www.seattlegenetics.com,
under the Investors section, or by calling 877-723-9521 (domestic) or
719-325-2138 (international). The access code is 9916080. A replay of
the discussion will be available beginning at approximately 8:30 a.m. PT
/ 11:30 a.m. ET today from Seattle Genetics' website or by calling
888-203-1112 (domestic) or 719-457-0820 (international), using access
code 9916080. The telephone replay will be available until 5:00 p.m. PT
/ 8:00 p.m. ET Wednesday, June 28, 2017.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: Hodgkin
lymphoma and non-Hodgkin lymphoma. Classical Hodgkin lymphoma is
distinguished from other types of lymphoma by the presence of one
characteristic type of cell, known as the Reed-Sternberg cell. The
Reed-Sternberg cell expresses CD30.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials in
CD30-expressing lymphomas, including three Phase 3 studies: the
completed ECHELON-1 trial in frontline classical Hodgkin lymphoma, the
completed ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing
ECHELON-2 trial in frontline mature T-cell lymphomas.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached
by a protease-cleavable linker to a microtubule disrupting agent,
monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary
technology. The ADC employs a linker system that is designed to be
stable in the bloodstream but to release MMAE upon internalization into
CD30-expressing tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA
for three indications: (1) regular approval for the treatment of
patients with classical Hodgkin lymphoma after failure of autologous
hematopoietic stem cell transplantation (auto-HSCT) or after failure of
at least two prior multi-agent chemotherapy regimens in patients who are
not auto-HSCT candidates, (2) regular approval for the treatment of
classical Hodgkin lymphoma patients at high risk of relapse or
progression as post-auto-HSCT consolidation, and (3) accelerated
approval for the treatment of patients with systemic anaplastic large
cell lymphoma (sALCL) after failure of at least one prior multi-agent
chemotherapy regimen. The sALCL indication is approved under accelerated
approval based on overall response rate. Continued approval for the
sALCL indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. Health Canada granted ADCETRIS
approval with conditions for relapsed or refractory Hodgkin lymphoma and
sALCL.

ADCETRIS was granted conditional marketing authorization by the European
Commission in October 2012 for two indications: (1) for the treatment of
adult patients with relapsed or refractory CD30-positive Hodgkin
lymphoma following autologous stem cell transplant (ASCT), or following
at least two prior therapies when ASCT or multi-agent chemotherapy is
not a treatment option, and (2) the treatment of adult patients with
relapsed or refractory sALCL.

In June 2016, the European Commission extended the current conditional
approval of ADCETRIS and approved ADCETRIS for the treatment of adult
patients with CD30-positive Hodgkin lymphoma at increased risk of
relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities
in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL.
See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the
terms of the collaboration agreement, Seattle Genetics has U.S. and
Canadian commercialization rights and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Seattle Genetics and Takeda are
funding joint development costs for ADCETRIS on a 50:50 basis, except in
Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) Global Important Safety Information

CONTRAINDICATIONS

ADCETRIS is contraindicated for patients with hypersensitivity to
brentuximab vedotin and its excipients. In addition, combined use of
ADCETRIS with bleomycin is contraindicated as it causes pulmonary
toxicity.

SPECIAL WARNINGS & PRECAUTIONS

Progressive multifocal leukoencephalopathy (PML): John Cunningham
virus (JCV) reactivation resulting in PML and death can occur in
patients treated with ADCETRIS. PML has been reported in patients who
received ADCETRIS after receiving multiple prior chemotherapy regimens.

Patients should be closely monitored for new or worsening neurological,
cognitive, or behavioral signs or symptoms, which may be suggestive of
PML. Suggested evaluation of PML includes neurology consultation,
gadolinium-enhanced magnetic resonance imaging of the brain, and
cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or
a brain biopsy with evidence of JCV. ADCETRIS dosing should be held for
any suspected case of PML and should be permanently discontinued if a
diagnosis of PML is confirmed.

Pancreatitis: Acute pancreatitis has been observed in patients
treated with ADCETRIS. Fatal outcomes have been reported. Patients
should be closely monitored for new or worsening abdominal pain, which
may be suggestive of acute pancreatitis. Patient evaluation may include
physical examination, laboratory evaluation for serum amylase and serum
lipase, and abdominal imaging, such as ultrasound and other appropriate
diagnostic measures. ADCETRIS should be held for any suspected case of
acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of
acute pancreatitis is confirmed.

Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal
outcomes, have been reported in patients receiving ADCETRIS. Although a
causal association with ADCETRIS has not been established, the risk of
pulmonary toxicity cannot be ruled out. New or worsening pulmonary
symptoms should be promptly evaluated and treated appropriately.

Serious infections and opportunistic infections: Serious
infections such as pneumonia, staphylococcal bacteremia, sepsis/septic
shock (including fatal outcomes), and herpes zoster, and opportunistic
infections such as Pneumocystis jiroveci pneumonia and oral
candidiasis have been reported in patients treated with ADCETRIS.
Patients should be carefully monitored during treatment for emergence of
possible serious and opportunistic infections.

Infusion-related reactions (IRR): Immediate and delayed IRR, as
well as anaphylaxis, have occurred with ADCETRIS. Patients should be
carefully monitored during and after an infusion. If anaphylaxis occurs,
administration of ADCETRIS should be immediately and permanently
discontinued and appropriate medical therapy should be administered. If
an IRR occurs, the infusion should be interrupted and appropriate
medical management instituted. The infusion may be restarted at a slower
rate after symptom resolution. Patients who have experienced a prior IRR
should be premedicated for subsequent infusions. IRRs are more frequent
and more severe in patients with antibodies to ADCETRIS.

Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS.
Patients with rapidly proliferating tumor and high tumor burden are at
risk of TLS. These patients should be monitored closely and managed
according to best medical practice.

Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both
sensory and motor. ADCETRIS-induced PN is typically cumulative and
reversible in most cases. Patients should be monitored for symptoms of
PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a
burning sensation, neuropathic pain, or weakness. Patients experiencing
new or worsening PN may require a delay and a dose reduction or
discontinuation of ADCETRIS.

Hematological toxicities: Grade 3 or Grade 4 anemia,
thrombocytopenia, and prolonged (equal to or greater than one week)
Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood
counts should be monitored prior to administration of each dose.

Febrile neutropenia: Febrile neutropenia has been reported.
Patients should be monitored closely for fever and managed according to
best medical practice if febrile neutropenia develops.

Stevens-Johnson syndrome (SJS): SJS and toxic epidermal
necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have
been reported. If SJS or TEN occurs, treatment with ADCETRIS should be
discontinued and appropriate medical therapy should be administered.

Gastrointestinal (GI) Complications: GI complications, some with
fatal outcomes, including intestinal obstruction, ileus, enterocolitis,
neutropenic colitis, erosion, ulcer, perforation and haemorragh, have
been reported. New or worsening GI symptoms should be promptly evaluated
and treated appropriately.

Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) have been reported. Serious cases of
hepatotoxicity, including fatal outcomes, have also occurred. Liver
function should be tested prior to treatment initiation and routinely
monitored in patients receiving ADCETRIS. Patients experiencing
hepatotoxicity may require a delay, dose modification, or
discontinuation of ADCETRIS.

Hyperglycemia: Hyperglycemia has been reported during trials in
patients with an elevated body mass index (BMI) with or without a
history of diabetes mellitus. However, any patient who experiences an
event of hyperglycemia should have their serum glucose closely
monitored. Anti-diabetic treatment should be administered as appropriate.

Renal and Hepatic Impairment: There is limited experience in
patients with renal and hepatic impairment. Available data indicate that
MMAE clearance might be affected by severe renal impairment, hepatic
impairment, and by low serum albumin concentrations. The recommended
starting dose in patients with hepatic impairment or severe renal
impairment is 1.2 mg/kg administered as an intravenous infusion over 30
minutes every 3 weeks. Patients with renal or hepatic impairment should
be closely monitored for adverse events.

Sodium content in excipients: This medicinal product contains a
maximum of 2.1 mmol (or 47 mg) of sodium per dose. To be taken into
consideration for patients on a controlled sodium diet.

INTERACTIONS

Patients who are receiving a strong CYP3A4 and P-gp inhibitor,
concomitantly with ADCETRIS may have an increased risk of neutropenia
and should be closely monitored. Co-administration of ADCETRIS with a
CYP3A4 inducer did not alter the plasma exposure of ADCETRIS but it
appeared to reduce plasma concentrations of MMAE metabolites that could
be assayed. ADCETRIS is not expected to alter the exposure to drugs that
are metabolized by CYP3A4 enzymes.

PREGNANCY: Women of childbearing potential should be using two
methods of effective contraception during treatment with ADCETRIS and
until 6 months after treatment. There are no data from the use of
ADCETRIS in pregnant women, although studies in animals have shown
reproductive toxicity. ADCETRIS should not be used during pregnancy
unless the benefit to the mother outweighs the potential risks to the
fetus. If a pregnant woman needs to be treated, she should be clearly
advised on the potential risk to the fetus.

LACTATION (breast-feeding): There are no data as to whether
ADCETRIS or its metabolites are excreted in human milk, therefore a risk
to the newborn/infant cannot be excluded. With the potential risk, a
decision should be made whether to discontinue breast-feeding or
discontinue/abstain from therapy with ADCETRIS.

FERTILITY: In nonclinical studies, ADCETRIS treatment has
resulted in testicular toxicity, and may alter male fertility. Men being
treated with this medicine are advised not to father a child during
treatment and for up to 6 months following the last dose.

Peripheral neuropathy (PN): ADCETRIS treatment causes a PN that is
predominantly sensory. Cases of motor PN have also been reported.
ADCETRIS-induced PN is cumulative. Monitor patients for symptoms of
neuropathy, such as hypoesthesia, hyperesthesia, paresthesia,
discomfort, a burning sensation, neuropathic pain or weakness and
institute dose modifications accordingly.

Anaphylaxis and infusion reactions: Infusion-related reactions,
including anaphylaxis, have occurred with ADCETRIS. Monitor patients
during infusion. If an infusion-related reaction occurs, interrupt the
infusion and institute appropriate medical management. If anaphylaxis
occurs, immediately and permanently discontinue the infusion and
administer appropriate medical therapy. Patients who experienced a
prior infusion-related reaction should be premedicated for subsequent
infusions. Premedication may include acetaminophen, an antihistamine,
and a corticosteroid.

Serious infections and opportunistic infections: Infections such as
pneumonia, bacteremia, and sepsis or septic shock (including fatal
outcomes) have been reported in patients treated with ADCETRIS.
Closely monitor patients during treatment for the emergence of
possible bacterial, fungal or viral infections.

Increased toxicity in the presence of severe renal impairment: The
frequency of ≥Grade 3 adverse reactions and deaths was greater in
patients with severe renal impairment compared to patients with normal
renal function. Avoid the use of ADCETRIS in patients with severe
renal impairment.

Increased toxicity in the presence of moderate or severe hepatic
impairment: The frequency of ≥Grade 3 adverse reactions and deaths was
greater in patients with moderate or severe hepatic impairment
compared to patients with normal hepatic function. Avoid the use of
ADCETRIS in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Serious cases of hepatotoxicity, including fatal
outcomes, have occurred with ADCETRIS. Cases were consistent with
hepatocellular injury, including elevations of transaminases and/or
bilirubin, and occurred after the first dose of ADCETRIS or
rechallenge. Preexisting liver disease, elevated baseline liver
enzymes, and concomitant medications may also increase the risk.

Monitor liver enzymes and bilirubin. Patients experiencing new,
worsening, or recurrent hepatotoxicity may require a delay, change in
dose, or discontinuation of ADCETRIS.

Progressive multifocal leukoencephalopathy (PML): JC virus infection
resulting in PML and death has been reported in ADCETRIS-treated
patients. First onset of symptoms occurred at various times from
initiation of ADCETRIS therapy, with some cases occurring within 3
months of initial exposure. In addition to ADCETRIS therapy, other
possible contributory factors include prior therapies and underlying
disease that may cause immunosuppression. Consider the diagnosis of
PML in any patient presenting with new-onset signs and symptoms of
central nervous system abnormalities. Hold ADCETRIS if PML is
suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicityEvents of noninfectious pulmonary toxicity
including pneumonitis, interstitial lung disease, and acute
respiratory distress syndrome, some with fatal outcomes, have been
reported. Monitor patients for signs and symptoms of pulmonary
toxicity, including cough and dyspnea. In the event of new or
worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation
and until symptomatic improvement.

Gastrointestinal (GI) complications: Fatal and serious GI
complications, including perforation, hemorrhage, erosion, ulcer,
intestinal obstruction, enterocolitis, neutropenic colitis, and ileus
have been reported in ADCETRIS-treated patients. Lymphoma with
preexisting GI involvement may increase the risk of perforation. In
the event of new or worsening GI symptoms, perform a prompt diagnostic
evaluation and treat appropriately.

Embryo-fetal toxicity: Based on the mechanism of action and findings
in animals, ADCETRIS can cause fetal harm when administered to a
pregnant woman. Females of reproductive potential should avoid
pregnancy during ADCETRIS treatment and for at least 6 months after
the final dose of ADCETRIS.

Takeda Pharmaceutical Company Limited is a global, research and
development-driven pharmaceutical company committed to bringing better
health and a brighter future to patients by translating science into
life-changing medicines. Takeda focuses its R&D efforts on oncology,
gastroenterology and central nervous system therapeutic areas plus
vaccines. Takeda conducts R&D both internally and with partners to stay
at the leading edge of innovation. New innovative products, especially
in oncology and gastroenterology, as well as our presence in Emerging
Markets, fuel the growth of Takeda. More than 30,000 Takeda employees
are committed to improving quality of life for patients, working with
our partners in health care in more than 70 countries. For more
information, visit http://www.takeda.com/news.

Additional information about Takeda is available through its corporate
website, www.takeda.com,
and additional information about Takeda Oncology, the brand for the
global oncology business unit of Takeda Pharmaceutical Company Limited,
is available through its website, www.takedaoncology.com.

About Seattle Genetics

Seattle Genetics is an innovative biotechnology company that develops
and commercializes novel antibody-based therapies for the treatment of
cancer. The company’s industry-leading antibody-drug conjugate (ADC)
technology harnesses the targeting ability of antibodies to deliver
cell-killing agents directly to cancer cells. ADCETRIS®
(brentuximab vedotin), the company’s lead product, in collaboration with
Takeda Pharmaceutical Company Limited, is the first in a new class of
ADCs commercially available globally in 67 countries for relapsed
classical Hodgkin lymphoma and relapsed systemic anaplastic large cell
lymphoma (sALCL). Seattle Genetics is also advancing enfortumab vedotin,
an ADC for metastatic urothelial cancer, in a planned pivotal trial in
collaboration with Astellas. Headquartered in Bothell, Washington,
Seattle Genetics has a robust pipeline of innovative therapies for
blood-related cancers and solid tumors designed to address significant
unmet medical needs and improve treatment outcomes for patients. The
company has collaborations for its proprietary ADC technology with a
number of companies including AbbVie, Astellas, Bayer, Celldex,
Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com

Forward Looking Statements for Seattle Genetics

Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS (brentuximab vedotin) as the foundation of care
for CD30-expressing lymphomas, anticipated publication of data from
ECHELON-1 and plans for submission for supplemental regulatory approval
to and obtaining regulatory approval from the FDA and other regulatory
authorities. Actual results or developments may differ materially from
those projected or implied in these forward-looking statements. Factors
that may cause such a difference include safety and/or efficacy results
of the ECHELON-1 trial in Hodgkin lymphoma that will not be sufficient
for publication or to gain marketing approval in the United States or
any other country, that we will be required to amend our submission for
marketing approval or that such submission will be refused or delayed.
In addition, our regulatory plans may change as a result of consultation
with the FDA or other regulatory authorities. More information about the
risks and uncertainties faced by Seattle Genetics is contained under the
caption “Risk Factors” included in the company’s Quarterly Report on
Form 10-Q for the quarter ended March 31, 2017 filed with the Securities
and Exchange Commission. Seattle Genetics disclaims any intention or
obligation to update or revise any forward-looking statements, whether
as a result of new information, future events or otherwise.

CAMBRIDGE, Mass. & OSAKA, Japan--(EON: Enhanced Online News)--Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the company will feature new clinical analyses and outcomes rese... more »